Mice are generally an excellent model of human biology with nearly identical metabolic pathways. In contrast, the 3000-fold difference in body mass causes huge differences in thermal physiology and energy homeostasis. Humans generally live in a thermoneutral environment, while mice live and are typically studied below thermoneutrality. A mouse housed singly at 22 °C devotes 42% of its energy expenditure to maintaining its body temperature; the corresponding value in humans is approximately 0%. Understanding this different physiology is important, allowing one to avoid incorrect application of mouse observations to humans. It also boosts elucidation of physiology that is subtle or difficult to study in humans. The goal is to understand thermal physiology and to use it to develop conditions under which mice better model humans. This is important for studying the effectiveness of drug treatments for metabolic diseases, like obesity and diabetes. Marc and Oksana discuss what thermoneutrality means in the mouse and the concept of the thermoneutral point. They also explore the effects of cold, hot, and near-thermoneutral environments on mouse energy expenditure, body temperature, and behavior.

1. Thermal Physiology: The Effects of
Environmental Temperatures on Energy
Expenditure in Mice
Oksana Gavrilova, PhD
Marc Reitman, MD, PhD
Staff Scientist, Core Director
Mouse Metabolism Core
NIDDK, NIH
oksanag@bdg10.niddk.nih.gov
Branch Chief, Senior Investigator
Diabetes, Endocrinology, and Obesity Branch
NIDDK, NIH
marc.reitman@nih.gov

2. Thermal Physiology: The Effects of
Environmental Temperatures on Energy
Expenditure in Mice
Marc Reitman, MD PhD
Oksana Gavrilova, PhD
Inside Scientific
January 20, 2022
No Disclosures
2022.01.20 Inside Scientific.pptx 2

3. 3
Why Study Energy Expenditure? Why mice?
 To discover and characterize fundamental physiology
 Mice are the most studied laboratory mammal
 Fundamental differences exist in energy expenditure between mice and humans
 Understand how mouse energy physiology applies to humans and to identify
conditions where mice are a better model of human physiology
 To inform anti-obesity drug design and development and increase probability of
success
Today:
 Review of indirect calorimetry
 Introduction to thermal biology
 Environmental temperature, body temperature, and energy expenditure

4. Putative ‘Causes’ of Obesity, 2015
1. agricultural policies
2. air conditioning
3. air pollution
4. antibiotic usage at early age
5. arcea nut chewing
6. artificial sweeteners
7. Asian tiger mosquitos
8. assortative mating
9. being a single mother
10. birth by C-section
11. built environment
12. celebrity chefs
13. chemical toxins, (endocrine disruptors)
14. child maltreatment
15. compulsive buying
16. competitive food sales in schools
17. consuming skim milk in preschool children,
18. consumption of pastries and chocolate (in Burkina
Faso),
19. decline in occupational physical activity,
20. delayed prenatal care
21. delayed satiety
22. depression
23. driving children to school
24. eating away from home
25. economic development (nutrition transition)
26. entering into a romantic relationship,
http://www.downeyobesityreport.com/2015/10/the-putative-104-causes-of-obesity-update/
27. epigenetic factors
28. eradication of Helicobacter pylori,
29. family conflict
30. family divorce
31. first-born in family
32. food addiction
33. food deserts
34. food insecurity
35. food marketing to children
36. food overproduction
37. friends
38. genetics
39. gestational diabetes
40. global food system,(international trade policies)
41. grilled foods
42. gut microbioata
43. having children for women
44. heavy alcohol consumption
45. home labor saving devices
46. hormones (insulin,glucagon,ghrelin),
47. hunger-response to food cues
48. high fructose corn syrup
49. interpersonal violence
50. lack of family meals
51. lack of nutritional education
52. lack of self-control
53. large portion sizes
54. living in crime-prone areas
55. low educational levels for women,
56. low levels of physical activity
57. low Vitamin D levels
58. low socioeconomic status
59. market economy
60. marrying in later life
61. maternal employment
62. maternal obesity
63. maternal over-nutrition during pregnancy,
64. maternal smoking
65. meat consumption
66. menopause
67. mental disabilities
68. no or short term breastfeeding,
69. non-parental childcare
70. outdoor advertising
71. overeating
72. participation in Supplemental Nutrition Assistance Program (formerly Food
Stamp Program)
73. perceived weight discrimination,
74. perception of neighborhood safety,
75. physical disabilities
76. prenatal maternal exposure to natural disasters,
77. poor emotional coping
78. sleep deficits
79. skipping breakfast
80. snacking
81. smoking cessation
82. spanking children
83. stair design
84. stress, artificial lighting, air
conditioning
85. sugar-sweetened beverages
86. taste for fat
87. trans fats
88. transportation by car
89. television set in bedrooms
90. television viewing
91. thyroid dysfunction
92. vending machines
93. virus
94. weight gain inducing drugs
95. working long hours
96. too much homework
97. insufficient body heat
98. imagining the smell of food
99. dust components
100. living with grandparents in China
101. estrogens
102. thermogenic adipocytes
103. prenatal exposure to cigarette smoke
104. starting college
Adapted from Morgan Downey; original link no longer current
4

5. 5
What is the Physiologic Basis for Obesity?
Intake / Expenditure Imbalance
Images from Wikipedia
1 2
3

6. 6
Components of Energy Expenditure
 Basal Metabolic Rate (BMR)
 Thermic Effect of Food (TEF)
 Physical Activity (PA)
 Cold-Induced Thermogenesis (CIT)

7. 7
Components of Energy Expenditure
 Basal Metabolic Rate (BMR)
 Thermic Effect of Food (TEF)
 Physical Activity (PA)
 Cold-Induced Thermogenesis (CIT)
 Measure energy expenditure with indirect calorimetry
 Measures rate of O2 consumption and CO2 production
 We also measure food intake and core body temperature by telemetry:
Room air To O2 and CO2
detectors
Metabolic cage
Activity monitor
Thermoregulated
chamber

8. 8
Indirect Calorimetry: Oxygen Consumption
Ratio of moles CO2 produced to O2 consumed
Carbohydrate (glucose)
C6H12O6 + 6O2  6CO2 + 6H2O + 673 kcal 112 kcal/mole O2
RQ=6/6=1.00
Fatty acid (palmitic acid)
C15H31COOH + 23O2  16CO2 + 16H2O + 2398 kcal 104 kcal/mole O2
RQ=16/23=0.70
Protein (alanine)
2CH3CH(NH)2COOH + 6O2  (NH)2CO + 5CO2 + 5H2O + 624 kcal
RQ=5/6=0.83 104 kcal/mole O2
Contribution of protein oxidation is rarely measured in mice

9. 9
Indirect Calorimetry: Respiratory Exchange Ratio (RER)
Ratio of moles CO2 produced to O2 consumed
Carbohydrate (glucose)
C6H12O6 + 6O2  6CO2 + 6H2O + 673 kcal 112 kcal/mole O2
RER=6/6=1.00
Fatty acid (palmitic acid)
C15H31COOH + 23O2  16CO2 + 16H2O + 2398 kcal 104 kcal/mole O2
RER=16/23=0.70
Protein (alanine)
2CH3CH(NH)2COOH + 6O2  (NH)2CO + 5CO2 + 5H2O + 624 kcal
RQ=5/6=0.83 104 kcal/mole O2

10. 10
Mouse Indirect Calorimetry (Some Thoughts)
 Report the total energy expenditure, TEE (e.g., as kcal/d/mouse)
 Reporting the vO2 and vCO2 does not add information above just the TEE & RER
 Report the RER
 Tells fuel source
 Average RER approximates Food Quotient (chow FQ=0.91, 60% fat FQ=0.79)
 Technical check: is RER biologically plausible?
 At steady state, TEE equals the metabolizable food intake (e.g., as kcal/d/mouse)
 Technical check: are TEE and food intake comparable?
 The calorimetry chamber is an unusual environment; ideally use 1-2 d acclimation
 5% TEE changes are biologically significant, but difficult to detect; 10% is detectable

11. 11
Body Weight and Metabolic Rate
Speakman JR (2013) Front Physiol doi: 10.3389/fphys.2013.00034
Tschop MH … (2012) Nat Meth 9:57-63
 If at all possible, study mice with the same body weight (and composition)
 One approach is to graph EE vs body weight (or lean body mass)
 Do not divide by body weight
 Always report the body weight for calorimetry experiments
 If possible, ANCOVA with lean mass and fat mass as independent predictors is best

12. 12
Incorporating Temperature in Calorimetry:
Ambient/Environmental Temperature (Ta)
Body Temperature (Tb)

13. David Deen © 2019
House Mouse as a Model System

14. 14

15. Thermal Biology: Effect of Body Size
Large
 e.g., Adult human (75 kg)
 Median Tb, 37.0 °C
 Diurnal rhythm (~1 °C)
 Body core insulated
 Most of the required heat is a metabolic
byproduct
 Small role for BAT (Brown Adipose Tissue)
 Physiology oriented to heat dissipation
(sweating, panting, vasodilation,
environment, behavior…)
 Tb* highly, tightly regulated; constant
Small
 e.g., Mouse (0.025 kg)
 Median Tb, 36.6 °C
 Diurnal rhythm (~1 °C)
 Body core poorly insulated
 Some heat from metabolism; more
needed
 Large role for BAT
 Physiology oriented to heat
conservation and generation (fur,
nesting, environment, behavior…)
 Tb highly, tightly regulated; can vary
15
*Tb = core body temperature

16. 16
Data Collection: Example of one mouse
0.0
0.3
0.5
0.8
1.0
319
338
357
376
395
414
433
452
471
490
509
528
547
566
585
604
623
642
661
680
699
718
737
756
775
794
813
832
851
870
889
908
927
946
965
984
1003
1022
1041
1060
1079
1098
1117
1136
1155
1174
1193
1212
1231
1250
1269
1288
1307
TEE
(kcal/h)
0
0.1
0.2
Food
intake
0
10
20
Physical
activity
34
36
38
T
b
(°C)
0.7
0.8
0.9
1
RQ
(CO
2
/O
2
)
0
10
20
30
T
a
(°C)
22 C 26°C 30°C 33°C 28°C 24°C 18°C 12°C 4°C
Day: 1 2 3 4 5 6 7 8 9
Ta
TEE
RER
Physical
activity
Tb
Food
intake

17. 17
*Ta = ambient temperature
Tb Regulation: Phase, Activity, and Ta*
Tb:
1.  in dark phase
2.  with activity
3.  (slight) with cold Ta
Abreu-Vieira G…(2015) Mol Metab 4:461-470

18. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta (Scholander / Kleiber plot)
18
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)
Scholander PF…(1950) Biol Bull 99:237-258
Kleiber MF, Dougherty JE (1934) J Gen Physiol 17:701-726
Kleiber MF (1975) The Fire of Life
Data: Abreu-Vieira G…(2015) Mol Metab 4:461-470
Mouse, light phase, after removal of physical activity and thermic effect of food

19. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta
19
 Light phase, after removal of physical activity and thermic effect of food
BMR
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)

20. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta
20
 Light phase, after removal of physical activity and thermic effect of food
BMR
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)

21. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta
21
 Light phase, after removal of physical activity and thermic effect of food
BMR
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)

22. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta
22
 Light phase, after removal of physical activity and thermic effect of food
BMR
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)

23. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta
23
 Light phase, after removal of physical activity and thermic effect of food
BMR
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)

24. 0.0
0.2
0.4
0.6
15 20 25 30 35 40
TEE
-
PAEE
-
TEF
(kcal/h)
Ta (°C)
Energy Expenditure vs Ta
24
 Light phase, after removal of physical activity and thermic effect of food
BMR
SEMs are hidden by symbols
Energy
Expenditure
(kcal/h)

25. 25
A Quantitative Description of Energy Expenditure in
the Mouse
0
0.2
0.4
0.6
0.8
1
4 8 12 16 20 24 28 32
Energy
Expenditure
(kcal/h)
Ta( C)
Physical activity
Thermic effect of food
Cold-induced thermogenesis
Basal Metabolic Rate
Ambient Temperature (°C)
Abreu-Vieira G…(2015) Mol Metab 4:461-470

26. 26
A Quantitative Description of Energy Expenditure in
the Mouse
0
0.2
0.4
0.6
0.8
1
4 8 12 16 20 24 28 32
Energy
Expenditure
(kcal/h)
Ta( C)
Physical activity
Thermic effect of food
Cold-induced thermogenesis
Basal Metabolic Rate
Ambient Temperature (°C)
Abreu-Vieira G…(2015) Mol Metab 4:461-470

27. 27
Wild Type
Clock Time
0600 1200 1800 2400 0600 1200
Body
Temperature
(C)
22
24
26
28
30
32
34
36
38
40
Fasting
Torpor: A Large Reduction in Tb
• Torpor requires:
Cool environment
Quiet environment
Inadequate food
 Full torpor can save a huge amount of energy
 This is normal biology for a mouse
Each red line is one mouse
Ta=22°C, 23g
Reitman ML (2018) FEBS Lett 592:2098-2107

28. 28
Under What Conditions are Mouse Studies Predictive
for Humans?
0
0.2
0.4
0.6
0.8
1
4 8 12 16 20 24 28 32
Energy
Expenditure
(kcal/h)
Ta( C)
Physical activity
Thermic effect of food
Cold-induced thermogenesis
Basal Metabolic Rate
Ambient Temperature (°C)

29. 29
Mouse: BMR TEF PAEE CIT .
30°C ‘thermoneutrality’ 60% 12% 25% 0%
22°C 33% 12% 13% 42%
‘Typical’ human: 70% 10% 20% 0%
Mouse vs. Human: Translational Implications
BMR, Basal Metabolic Rate
TEF, Thermic Effect of Food
PAEE, Physical Activity Energy Expenditure
CIT, Cold-Induced Thermogenesis
Would studying mice at thermoneutrality be more
predictive of the effect of human obesity drug efficacy?

30. 30
2-4,Dinitrophenol (DNP) -
+ H+
pKa = 4.4
H
DNP
DNP-
DNP
DNP-
 DNP is a chemical uncoupler (works in every tissue)
 Munitions industry (1917): DNP increases metabolic rate
 Early 1930s: used by over 100,000 people for weight loss
 Use waned in the late 1930s due to adverse side-effects
(death, cataracts, neuropathy, hyperthermia)
 Currently (ab)used by body builders
Modified from: Krauss S… (2005) NatRevMolCellBiol 6:248-261, Blaikie FH…(2006) BiosciRep 26:231-243

31. 31
DNP effect vs vehicle at:
Parameter 30°C 22°C
Ucp1 RNA, BAT capacity  
Total energy expenditure  no change
Food intake no change no change
Body weight, adiposity  no change
Glucose tolerance improved not improved
Ambient Temperature (ºC)
20 24 28 32
Metabolic
Rate
(%
of
30ºC)
0
100
200
DNP
Resting
Adaptive
C57BL/6J mice
DNP ~89 mg/kg/d p.o.
Treatment for 2 months
High fat diet

32. 32
DNP effect vs vehicle at:
Parameter 30°C 22°C
Ucp1 RNA, BAT capacity  
Total energy expenditure  no change
Food intake no change no change
Body weight, adiposity  no change
Glucose tolerance improved not improved
Ambient Temperature (ºC)
20 24 28 32
Metabolic
Rate
(%
of
30ºC)
0
100
200
DNP
Resting
Adaptive
C57BL/6J mice
DNP ~89 mg/kg/d p.o.
Treatment for 2 months
High fat diet

33. 33
Goldgof M, Xiao C … (2014) JBC 289:19341-19350
Ambient Temperature (ºC)
20 24 28 32
Metabolic
Rate
(%
of
30ºC)
0
100
200
DNP
Resting
Adaptive
DNP effect vs vehicle at:
Parameter 30°C 22°C
Ucp1 RNA, BAT capacity  
Total energy expenditure  no change
Food intake no change no change
Body weight, adiposity  no change
Glucose tolerance improved not improved
C57BL/6J mice
DNP ~89 mg/kg/d p.o.
Treatment for 2 months
High fat diet

34. Mice Adapt to Ambient Temperature
34
 It takes 1-2 weeks of cold exposure for full browning or beiging of adipose tissue and
a similar time to reverse with warm exposure Cannon B & Nedergaard J (2004) Physiol Rev 84:277-359
 Warm-adapted mice may not tolerate acute cold exposure, but do tolerate it if
gradually adapted to the cold Golozoubova V…(2001) FASEB J 15:2048-2050
 Central Tb regulation adapts to warm (or reverses) in 3-5 days Piñol RA…(2021) Cell Met 33:1389-1403

35. 35
 Goal: Maximize drug effect to increase energy expenditure
 Mice housed below thermoneutrality so BAT is active
 Moved to 30 ºC to reduce sympathetic activation of BAT
 Drug given hours (not days) after start of 30 ºC
 Examples of drugs: β-adrenergic agonists, melanocortin agonists, BRS3 agonists
Sensitive Assay for BAT Activation
Ambient Temperature (ºC)
20 24 28 32
Metabolic
Rate
(%
of
30ºC)
0
100
200
DNP
Resting
Adaptive
Drug

36. 36
Škop V, Xiao C … (2021) Mol Met 53:101332
Used for measurement of individual mouse food intake, metabolic rate, Tb
Precludes huddling, fighting, group interactions
Guidelines suggest avoiding whenever possible
Unclear if more stressful
Social Thermoregulation: Effect of Group Housing
Not commonly used in metabolic and Tb studies
Allows huddling, fighting, group interactions

37. 37
Škop V, Xiao C … (2021) Mol Met 53:101332
Social Thermoregulation: Effect of Group Housing

38. 38
Škop V, Xiao C … (2021) Mol Met 53:101332
Social Thermoregulation: Effect of Group Housing

39. 39
Škop V, Xiao C … (2021) Mol Met 53:101332
Social Thermoregulation: Effect of Group Housing
 Single housing increases heat loss and amplifies the effects of
fasting or a cold environment.
 Male and female mice use different thermoregulatory
strategies to respond to single housing.
 Single housing is more sensitive than group housing for
detecting thermal physiology phenotypes.

40. What About the Upper End of the Thermoneutral
Zone ?
40

41. 41
Energy Use vs Ambient Temperature (Ta):
Energy Cost of Adapting to the Environment
Hill RW … (2013) PLoS One 8:e76238

42. 42
Energy Use vs Ambient Temperature (Ta):
Energy Cost of Adapting to the Environment
Hill RW … (2013) PLoS One 8:e76238

43. What About the Upper End of the Mouse
Thermoneutral Zone (TNZ)?
43
 Prior studies: None incorporated detailed analysis of Tb
Herrington LP (1940) Am. J. Physiol. 129,123–139
Pennycuik PR (1967) Aust. J. Exp. Med. Sci. 45,331–346
Gordon CJ (1985) Physiol. Behav. 34,687-690
Oufara S et al. (1987) Am. J. Physiol. 253,R39–R45
Klaus S et al. (1998) Am. J. Physiol. 274,R287–R293
Meyer CW et al. (2004) Obesity Res. 12,1509-1518

44. The Mouse Dark Phase TNZ is a Thermoneutral Point
Vojtěch Škop… (2020) Cell Rep 31:107501
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
TNPL
Mouse
resting phase
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
TNPD
Mouse
active phase
~29 ºC
~33 ºC
Summary
1. In dark/active phase, mice have a TNPD, coincident with the TNZ (TNZ is a point)
Mouse
Light/Resting
Mouse
Dark/Active
Define the “Thermoneutral Point” or TNP:
“Discrete ambient temperature, below which
energy expenditure increases and above
which core body temperature increases”

45. The Mouse Thermoneutral Point Changes Diurnally
Vojtěch Škop… (2020) Cell Rep 31:107501
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
TNPL
Mouse
resting phase
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
TNPD
Mouse
active phase
~29 ºC
~33 ºC
Summary
1. In dark/active phase, mice have a TNPD, coincident with the TNZ (TNZ is a point)
2. In light/resting phase, mice have a TNPL, where regulated Tb increase starts;
The second breakpoint in the light phase is at the TNPD, above which Tb regulatory
mechanisms are overwhelmed. Replicated in multiple models.
Mouse
Light/Resting
Mouse
Dark/Active

46. The Mouse Thermoneutral Point Changes Diurnally
Vojtěch Škop… (2020) Cell Rep 31:107501
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
Human
active phase
TNZ
~29 ~33
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
TNPD
20 30 40
0
100
200
300
34
36
38
40
Ambient Temperature (ºC)
Energy
Expenditure
(%)
Body
Temperature
(ºC)
TNPL
Human
Light/Active
Mouse
Summary
1. In dark/active phase, mice have a TNPD, coincident with the TNZ (TNZ is a point)
2. In light/resting phase, mice have a TNPL, where regulated increase Tb starts;
The second breakpoint in the light phase is at the TNPD, above which Tb regulatory
mechanisms are overwhelmed
3. Humans do not have a TNP

47. Implications: Studying Mice ‘at Thermoneutrality’
47
 Studying mice ‘at thermoneutrality’ is not feasible
 Having a TNPL of 29 ºC and a TNPD of 33 ºC is NOT a TNZ of 29 to 33 ºC
 So how should one choose a mice experiment Ta most likely to be
predictive of human physiology?
 Keijer/Speakman suggest 25-27 ºC
 Cannon/Nedergaard suggest 28-30 ºC
 Propose using a Ta of ~ 28 to 29 ºC
 Want to stay below TNP at all times (light and dark)
 Allows mouse to use its thermoregulation (unlike humans, mice typically live
below thermoneutrality, especially in dark/active phase)
 Being near the TNP minimizes cold-induced thermogenesis
 Propose: State the actual Ta used and avoid ‘thermoneutrality’
Speakman JR, Keijer J (2013) Mol Metab 2:5-9
Fischer AW … (2018) Mol Metab 7:161-170
Keijer J … (2019) Mol Metab 25:168-176
Fischer AW … (2019) Mol Metab 26:1-3

48. Implications: Prior studies at 30 ºC
 Prior studies typically used a Ta of 30 ºC as ‘thermoneutrality’
 30 ºC is above thermoneutrality during light phase
 30 ºC is below thermoneutrality during dark phase
 How to interpret those results?
 Increasing Tb increases inflammatory/immune actions
 Poorly understood physiology occurs in mice housed at a Ta of 30 ºC
 Increased obesity on a high-fat diet
 Ucp1-/- mice become obese
 Dio2-/- mice become obese
 Fgf13+/- mice become obese
 Food intake did not increase to match energy expenditure caused by DNP
 If you have a new mouse you want to study, ideally you need to know
Feldmann HM … (2009) Cell Metab 9:203-209
Feldmann HM … (2009) Cell Metab 9:203-209
Castillo M … (2011) Diabetes 60:1082-1089
Goldgof M … (2014) J Biol Chem 289:19341-19350
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Mice are not just small humans when it comes to thermal biology
48

49. Environmental Temperature and Obesity
49
 Mice are typically studied at ~22°C, well below thermoneutrality, while
humans are usually at thermoneutrality
 Drugs can have different effects when studied at thermoneutrality vs
below it
 The mouse thermoneutral zone is a thermoneutral point that changes
diurnally by ~4 °C
 We propose considering Tb in the definition of thermoneutrality
 Mice have thermoneutral points, not a thermoneutral zone, which must
be incorporated into how mice are used to model human physiology
 The thermal physiology of humans and mice is qualitatively different

50. 50
Reitman, DEOB, NIDDK:
 Soumya Kulkarni
 Ramón Piñol
 Vojtěch Škop
 Yu-Hsiang Tu
 Cuiying Xiao
MMC, NIDDK
 Oksana Gavrilova
 Shalini Jain
 Naili Liu
 Beth Lute
 Yinyan Ma
Acknowledgements
DEOB, NIDDK
 Michael Krashes
 Chia Li
MRS, LBC, NIDDK
 Ken Jacobson
 Dilip Tosh
LBM, NIDDK
 Kevin Hall
 Juen Guo
Former:
 Gustavo Abreu-Vieira
 Jesse Carlin
 Margalit Goldgof
 Colleen Hadley
 Dalya Lateef
 Allison Mogul
 Haley Province
 Yann Ravussin
 Atreyi Saha
 Brandon Tan
 Sebastian Zahler

51. Extras after here
51
 xx
Questions?

52. Thank you for participating!
Oksana Gavrilova, PhD
Marc Reitman, MD, PhD
Staff Scientist, Core Director
Mouse Metabolism Core
NIDDK, NIH
oksanag@bdg10.niddk.nih.gov
Branch Chief, Senior Investigator
Diabetes, Endocrinology, and Obesity Branch
NIDDK, NIH
marc.reitman@nih.gov
CLICK HERE to learn more and
watch the webinar